rs11205387

Positions:

• chr1-150510262-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004425.4(ECM1):​c.385+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,337,306 control chromosomes in the GnomAD database, including 52,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5217 hom., cov: 32)
  • Exomes 𝑓: 0.28 (47369 hom.)
• Consequence: ECM1 NM_004425.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65

Genes affected

ECM1 (HGNC:3153): (extracellular matrix protein 1) This gene encodes a soluble protein that is involved in endochondral bone formation, angiogenesis, and tumor biology. It also interacts with a variety of extracellular and structural proteins, contributing to the maintenance of skin integrity and homeostasis. Mutations in this gene are associated with lipoid proteinosis disorder (also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease) that is characterized by generalized thickening of skin, mucosae and certain viscera. Alternatively spliced transcript variants encoding distinct isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-150510262-G-A is Benign according to our data. Variant chr1-150510262-G-A is described in ClinVar as [Benign]. Clinvar id is 1258875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ECM1	NM_004425.4	c.385+80G>A		intron_variant		ENST00000369047.9	NP_004416.2
ECM1	NM_001202858.2	c.466+80G>A		intron_variant			NP_001189787.1
ECM1	NM_022664.3	c.385+80G>A		intron_variant			NP_073155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ECM1	ENST00000369047.9	c.385+80G>A		intron_variant		1	NM_004425.4	ENSP00000358043	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39143 AN: 152024 Hom.: 5209 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.279 AC: 331045 AN: 1185164 Hom.: 47369 Cov.: 18 AF XY: 0.281 AC XY: 169038 AN XY: 601824

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.257 AC: 39173 AN: 152142 Hom.: 5217 Cov.: 32 AF XY: 0.260 AC XY: 19305 AN XY: 74372

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.281

Alfa AF: 0.274 Hom.: 5751

Bravo AF: 0.258

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.61
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11205387; hg19: chr1-150482738; COSMIC: COSV60872532; COSMIC: COSV60872532;